Optical Sensing of Dysplasia and Aneuploidy at Upper GI Endoscopy Objectives: 1. To establish the real-world feasibility of using ESS integrated biopsy tools for in vivo sensing of dysplasia and aneuploidy in BE. a. Utilizing integrated ESS-optical forceps, we will develop a diagnostic algorithm and determine its sensitivity, specificity, and negative predictive value for classifying ESS spectra in the detection of dysplasia and aneuploidy. b. We will develop a next-generation biopsy forcep that can seamlessly scan and assess larger mucosal areas in order to hone in on foci of flat, invisible dysplasia and/or aneuploidy within a Barrett's segment. 2. To prospectively validate the diagnostic algorithm (based on the results first objective) in a cohort of Barrett's patients to establish whether ESS-guided biopsy improves per- biopsy dysplasia and/or aneuploidy detection rates over standard random surveillance biopsies. The potential benefit of this research is the validation of this integrated diagnostic biopsy tool for upper GI endoscopy. Use of the device could cost-effectively enhance Barrett's Esophagus screening strategies and patient outcomes. Research design: This will be a two-phase prospective study. Since tissue type cannot be determined with standard endoscopic views and the ESS is a computerized reading, subjects will not need to be randomized and endoscopists need not be blinded. The pathologists will be blinded to the ESS reading and aneuploidy analysis results. Methodology: Candidate subjects for this study will be drawn from an extant pool of patients who are scheduled for an endoscopy of the esophagus to determine whether they have pathologic conditions, or to determine whether their disease has advanced. Upon obtaining a signed Informed Consent, all patients will receive standard treatment i.e., routine esophageal endoscopy with random multiple physical biopsies using a predetermined geometric pattern as indicated for their care. Prior to the standard physical biopsy, an optical biopsy will be taken of the exact same tissue with the same forceps. The FDA approved device fitted with custom optics will take a 2 second reading consisting of flashes of white light and measurement of light reflected and refracted from the tissue. The forceps device is designed to then be able to biopsy the exact tissue measured by ESS. The tissue will then be sent for pathology in standard fashion with an additional independent pathologist review to confirm histology. In the event of a disagreement a third pathologist will review the slides. The outcome will be the correlation of the ESS reading and the tissue pathology. For the detection of aneuploidy, DNA histograms representing the frequency distribution of the DNA index values of the population of cells will be constructed using the ACIS DNA ploidy software with lesions classified as diploid, tetraploid or aneuploid. ESS spectra and the corresponding DNA index will be correlated as above for grades of dysplasia. In phase two of the study, the algorithm trained with the data collected in the previous phase will be tested for real-time detection of dysplasia to increase the per-biopsy yield of dysplastic and/or aneuploidy tissue. PUBLIC HEALTH RELEVANCE: The potential benefit of this research is the validation of an integrated diagnostic biopsy tool for upper GI endoscopy. This device could cost-effectively enhance Barrett's Esophagus screening & surveillance strategies. The potential clinical benefits of using elastic scattering spectroscopy for detection of Barrett's Esophagus in Veteran patients are: 1. An increase in the endoscopist's accuracy in finding diseased tissue by the use of a smart biopsy system rather than a random biopsy approach. 2. The potential of real-time and in vivo diagnosis. 3. Earlier treatment of Barrett's because diseased tissue can be identified before it is visually detectable at endoscopy with better patient outcomes. 5. Reductions in the number of biopsies of inconsequential normal tissue and the associated cost.